Corneal ulceration and corneal "melting" may be associated with bacterial, viral, and fungal eye disease; it is an integral factor in alkali burns and other systemic diseases. The producton of collagenases by infectious agents or by a variety of host tissues (polymorphonuclear leukocytes, corneal epithelium, or conjunctiva) constitutes a special mechanism of ulceration. The principle focus of this research is to isolate various collagenases and to purify them sufficiently to permit characterization of certain biochemical properties such as substrate utilization and specificity. The second goal of this project is to utilize a set of chemically designed inhibitors to neutralize their enzymatic action based upon a knowledge of their catalytic site requirements. This latter objective is assisted in part by a companion grant (NEI EYOO969) in which these compounds are being synthesized.